Structural and functional denervation of human detrusor after spinal cord injury

Marcus J. Drake, Petter Hedlund, Ian W. Mills, Rachel Mccoy, Gordon Mcmurray, Brian P. Gardner, Karl Erik Andersson, Alison F. Brading

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

The bladder receives an extensive nerve supply that is predominantly cholinergic, but several putative transmitters are present, some of which are colocalized. Previous studies have shown increased levels of sensory nerves, reduced inhibitory transmitters, and structural and functional changes in the excitatory input in unstable bladder conditions. The present study compared the end-organ nerve supply to the bladder in spinal cord injury (SCI) with uninjured controls. Acetylcholinesterase histochemistry and double-label immunofluorescence were used to investigate neurotransmitter content, with confocal laser scanning microscopy to assess colocalization. Organ bath studies provided functional correlates for the structural changes in the excitatory innervation. Control samples had dense innervation of the detrusor containing a diverse range of transmitters. Hyperreflexic SCI samples showed patchy denervation, and areflexic SCI samples were diffusely denervated. Vasoactive intestinal polypeptide-, neuropeptide Y-, neuronal nitric oxide synthase-, and galanin-immunoreactive nerve fibers were reduced from frequent or moderately frequent to infrequent or very infrequent in SCI. Calcitonin gene-related peptide-immunoreactive fibers were infrequent in controls and SCI samples. Patterns of colocalization were unchanged, but significantly fewer fibers expressed more than one transmitter. The subepithelial plexus was markedly reduced and several of the smaller coarse nerve trunks showed no immunoreactivity to the transmitters assessed. There was no reduction in sensitivity to electrical field stimulation of intrinsic nerves in SCI, but the maximum force generated by each milligram of bladder tissue and the peak force as a proportion of the maximum carbachol contraction were significantly reduced and the responses were protracted. There was no significant functional atropine-resistant neuromuscular transmission in controls or SCI. The reported findings have clinical implications in the management of chronic SCI and development of new treatments.

Original languageEnglish
Pages (from-to)1491-1499
Number of pages9
JournalLaboratory Investigation
Volume80
Issue number10
Publication statusPublished - 2000

Fingerprint

Denervation
Spinal Cord Injuries
Urinary Bladder
Galanin
Nitric Oxide Synthase Type I
Calcitonin Gene-Related Peptide
Neuropeptide Y
Vasoactive Intestinal Peptide
Carbachol
Acetylcholinesterase
Baths
Atropine
Nerve Fibers
Confocal Microscopy
Cholinergic Agents
Electric Stimulation
Fluorescent Antibody Technique
Neurotransmitter Agents

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Drake, M. J., Hedlund, P., Mills, I. W., Mccoy, R., Mcmurray, G., Gardner, B. P., ... Brading, A. F. (2000). Structural and functional denervation of human detrusor after spinal cord injury. Laboratory Investigation, 80(10), 1491-1499.

Structural and functional denervation of human detrusor after spinal cord injury. / Drake, Marcus J.; Hedlund, Petter; Mills, Ian W.; Mccoy, Rachel; Mcmurray, Gordon; Gardner, Brian P.; Andersson, Karl Erik; Brading, Alison F.

In: Laboratory Investigation, Vol. 80, No. 10, 2000, p. 1491-1499.

Research output: Contribution to journalArticle

Drake, MJ, Hedlund, P, Mills, IW, Mccoy, R, Mcmurray, G, Gardner, BP, Andersson, KE & Brading, AF 2000, 'Structural and functional denervation of human detrusor after spinal cord injury', Laboratory Investigation, vol. 80, no. 10, pp. 1491-1499.
Drake MJ, Hedlund P, Mills IW, Mccoy R, Mcmurray G, Gardner BP et al. Structural and functional denervation of human detrusor after spinal cord injury. Laboratory Investigation. 2000;80(10):1491-1499.
Drake, Marcus J. ; Hedlund, Petter ; Mills, Ian W. ; Mccoy, Rachel ; Mcmurray, Gordon ; Gardner, Brian P. ; Andersson, Karl Erik ; Brading, Alison F. / Structural and functional denervation of human detrusor after spinal cord injury. In: Laboratory Investigation. 2000 ; Vol. 80, No. 10. pp. 1491-1499.
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